Hyperbilirubinemia or jaundice affects nearly half of all newborn infants, and because bilirubin can be toxic to newborns, the management of neonatal jaundice is one of the most common problems in pediatrics. Our objective is improvement of the safety and efficacy of visible light phototherapy, the most common method used to reduce the serum concentrations of bilirubin in jaundiced newborn infants. Recent work has shown that the most important pathway for bilirubin elimination during phototherapy is production and secretion of a structural isomer of bilirubin, designated lumirubin. Traditional recommendations for phototherapy are based on maximizing the production of bilirubin photooxidation products or configurational isomers, which were previously thought to be the main route for pigment elimination. Not only would these recommendations fail to optimize phototherapy, but they result in significant serum concentrations of configurational isomers, of unknown toxicity, and also involve the use of phototherapy lamps which emit considerable irradiation below 450 nm, a portion of the visible spectrum which has been shown to damage DNA in vitro. Recent work has shown that wavelengths of light greater than 450 nm are the most effective in the production of lumirubin, and also that the binding of naturally-occurring fatty acids to albumin- bilirubin complexes increases the production of lumirubin by as much as 300%. We will investigate the factors controlling bilirubin structural isomerization and competing photochemical reactions, both in vitro and in vivo, using a new HPLC system which provides rapid quantitative analysis of bilirubin and its photoproducts. The specific aims are to determine the effect of physiological changes in the binding of bilirubin to albumin on the photochemistry of bilirubin in vitro and in vivo, to characterize the binding of lumirubin to human serum albumin, to evaluate the potential toxicity of bilirubin photoisomers, and to study the effectiveness of several light sources for the in vivo production of lumirubin and for the treatment of jaundiced infants. The fundamental understanding of the photochemistry of bilirubin provided by the work proposed in this application may lead to ways of minimizing potential adverse effects of phototherapy and at the same time increasing lumirubin production and thereby improving the effectiveness of phototherapy.